The objective of this project is to determine the mechanisms of "spontaneous" and carcinogen-induced malignant transformation in cultured cells. Emphasis is on the development of culture systems utilizing human epithelial cells to study the interaction of chemical carcinogens and viruses with cellular DNA, to define fundamental cytologic and other characteristics of carcinogenic change, and to provide quantifiable criteria of malignant conversion. The project this year consists of the following four studies: 1. Light-induced chromatid damage in relation to DNA repair and malignant transformation in culture. 2. Differential sensitivity of normal cells and their neoplastic derivatives to the lethal action of hydrogen peroxide. 3. Development of human epithelial cell systems for carcinogenesis studies. 4. Evaluation of in vivo assay techniques for determining the neoplastic state of cultured cells.